Diazepam inhibits acute innate and ongoing adaptive inflammatory responses

FALCÓN CRISTIAN R.; MONFERRAN, CLARA G.; CERVI LAURA C.; ROTH GERMAN A.

Mar del Plata

Congreso; LXII Reunión Anual de la Sociedad Argentina de Inmunología (SAI) y LIX Reunión Científica de la Sociedad Argentina de Investigación Clínica (SAIC); 2014

SAIC - SAI

In addition to the central GABAergic receptors described for benzodiazepines, peripheral-type benzodiazepine receptor (PBR) was also identified for these molecules in immune cells, such as macrophages and lymphocytes. PBR activation was reported to decrease inflammatory immune responses. In this regard, we previously demonstrated that Diazepam (Dz) decreases LPS-induced dendritic cell activation and their ability to induce allogeneic responses, thus preventing the initiation of immune responses. In this work we demonstrate that Dz is able to diminish acute innate and adaptive ongoing inflammatory responses in vivo. For this, we treated C57BL/6 mice with Dz (2mg/Kg) at days 0, 2 and 4, and 12 h after the last treatment the mice were injected (i.p.) with 800 μg de LPS. Dz was able to prevent LPS-induced death and inhibit the IL-6 secretion (p<0.001) by peritoneal cells favoring IL-10 production (p<0.002). On the other hand, mice with MOG-induced experimental autoimmune encephalomyelitis (EAE) were treated (i.p.) with Dz (2mg/Kg) on alternate days starting when the clinical score 1 was reached. The treatment dramatically decreased EAE progression evidenced by visible clinical signs which did not increase from the beginning of the injections. Moreover, Dz treatment impaired MOG-specific IL-17 (p<0.03) and IFN-γ (p<0.001) production by cells of draining lymphatic nodes. Together these data suggest that Dz is able to suppress both, innate and adaptive dependent inflammatory responses, which could be an interesting tool to modulate undesirable autoimmune responses as those occurring in multiple sclerosis.